Submission Details

The TRAPPC6B gene is located on chromosome 14 at 14q21.1 and encodes the trafficking protein particle complex, subunit 6B protein, a core subunit of TRAPP II and TRAPP III complexes. TRAPPC6B was first reported in relation to autosomal recessive neurodevelopmental disorder with microcephaly, epilepsy and brain atrophy (NEDMEBA) in 2018 (Marin-Valencia et al., PMID: 28626029). NEDMEBA is characterized by severe intellectual disability, global developmental delay, microcephaly and short stature. Evidence supporting this gene-disease relationship includes case-level data, segregation data and experimental evidence. To date, 6 splice site variants and 9 nonsense variants, including 10 unique and 5 recurrent variants in 38 patients have been reported in four publications. Two splice site variants and 4 nonsense variants from four publications are included in this curation (PMID 28626029, 28397838, 31687267, 37713627). This gene-disease relationship is supported by experimental evidence including functional alteration and rescue in patient cells, as well as data from zebrafish and drosophila models showing partial recapitulation of phenotype (PMID 37713627, 28626029). In summary, there is definitive evidence to support the relationship between TRAPPC6B and autosomal recessive NEDMEBA. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date November 19, 2024 (SOP Version 11).